chr3-27721936-G-GCGTCGC

Variant names:

• chr3-27721936-G-GCGTCGC
• NM_001278182.2:c.358_359insGCGACG

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

The NM_001278182.2(EOMES):​c.358_359insGCGACG​(p.Ala119_Ala120insGlyAsp) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000824 in 1,213,122 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: EOMES NM_001278182.2 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

Genes affected

EOMES (HGNC:3372): (eomesodermin) This gene belongs to the TBR1 (T-box brain protein 1) sub-family of T-box genes that share the common DNA-binding T-box domain. The encoded protein is a transcription factor which is crucial for embryonic development of mesoderm and the central nervous system in vertebrates. The protein may also be necessary for the differentiation of effector CD8+ T cells which are involved in defense against viral infections. A similar gene disrupted in mice is shown to be essential during trophoblast development and gastrulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_001278182.2

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EOMES	NM_001278182.2	c.358_359insGCGACG	p.Ala119_Ala120insGlyAsp	conservative_inframe_insertion	Exon 1 of 6	ENST00000449599.4	NP_001265111.1
EOMES	NM_005442.4	c.358_359insGCGACG	p.Ala119_Ala120insGlyAsp	conservative_inframe_insertion	Exon 1 of 6		NP_005433.2
EOMES	XM_005265510.5	c.358_359insGCGACG	p.Ala119_Ala120insGlyAsp	conservative_inframe_insertion	Exon 1 of 7		XP_005265567.1
EOMES	NM_001278183.2	c.-5+493_-5+494insGCGACG		intron_variant	Intron 1 of 5		NP_001265112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EOMES	ENST00000449599.4	c.358_359insGCGACG	p.Ala119_Ala120insGlyAsp	conservative_inframe_insertion	Exon 1 of 6	1	NM_001278182.2	ENSP00000388620.1
EOMES	ENST00000295743.8	c.358_359insGCGACG	p.Ala119_Ala120insGlyAsp	conservative_inframe_insertion	Exon 1 of 6	1		ENSP00000295743.4
EOMES	ENST00000461503.2	c.-5+493_-5+494insGCGACG		intron_variant	Intron 1 of 5	2		ENSP00000487112.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 8.24e-7 AC: 1 AN: 1213122 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 591022

Gnomad4 AFR exome AF: 0.0000421

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-27763427;